synthesis and pharmacological evaluation of 1,3,4-thiadiazole bearing pyrimidine derivatives as stat3 inhibitor for treatment of breast cancer

Novel scaffold of 1,3,4-thiadiazolo-(3,2-α)-pyrimidine-6-carbonitrile derivatives was designed based on sar of known inhibitors of stat3 and synthesised using optimized reaction condition. these compounds were subjected to in silico studies using discovery studio software and evaluated for their anticancer activity. a docking study of the newly synthesized compounds was performed; the results showed good binding mode in the active site of stat3 enzyme. among the synthesized compounds, compounds b4 and b5 show binding similar to standard drug static. the cellular evaluation indicates that the anticancer activity of compounds b4, b5 (ic50 = 54.51 ± 2.02 µg/ml and 45.43 ± 1.05 µg/ml, respectively) is active against mda-mb-232 cell line and compounds b5, b7 (ic50 = 40.21 ± 3.01 µg/ml, 56.77 ± 2.96 µg/ml, respectively) are most active against mcf-7 cell lines. from in vitro result, compound b5 subjected to acute oral toxicity studies by oecd 423 guidelines and in vivo anti-cancer studies carried out using dmba-induced model.